Therapeutic Vaccination and Immune Modulation - New Treatment Strategies for the MDR Tuberculosis Pandemic
Status:
Unknown status
Trial end date:
2019-09-01
Target enrollment:
Participant gender:
Summary
Tuberculosis (TB) is a global challenge and for the increasing epidemic of multi-drug
resistant (MDR)-TB there is restricted treatment options. This calls for research of new
immune-modulating treatment strategies that can strengthen the patients immune system to
better fight the TB bacteria. The pro-inflammatory, but still immunosuppressive mediator
prostaglandin E2 (PGE2) is produced by cyclooxygenase-2 (COX-2) in inflamed infected tissue.
Studies from both human and animal models show that COX-2 inhibitors (COX-2i) can improve the
immune system and strengthen vaccines responses.
Hypothesis
1. A hyperactive COX-2/PGE2 signal system in active TB causes down-regulated immune
responses that favour TB survival, but this can be abrogated by COX-2i.
2. TB-specific immunisation with targeted antigens presented as a therapeutic TB vaccine
and enhanced by COX-2i will improve immune-mediated host clearance of TB.
3. Combinations of COX-2i and a therapeutic TB vaccine to conventional anti-TB chemotherapy
offer new treatment modalities for TB, including MDR/XDR-TB.
Approach to test the hypothesis
1. Study design: 4-arm, open and randomized clinical intervention trial of patients
starting treatment for active TB in specialized Norwegian TB centres and where two arms
will receive the COX-2i etoricoxib with and without a TB vaccine, one arm vaccine only
and the last arm serve as control receiving only standard anti-TB therapy. For safety
precautions, only patients bearing sensitive TB strains are included and study arms will
be sequentially introduced.
2. In a mouse model examine in more detail the effects of reversion of chronic inflammation
with COX-2i locally in tissue and the interplay with TB vaccine responses, immune
regulation, correlates of protection and survival in a well-characterized model for
TB-exposed mice.
Phase:
Phase 1
Details
Lead Sponsor:
Anne Margarita Dyrhol Riise
Collaborators:
Haukeland University Hospital Statens Serum Institut University of Oslo